Hepatocellular carcinoma (HCC) is characterized by a high mortality and early diagnosis and treatment are critically needed. Ang II type 1 receptor (AT1R) has recently emerged as a potential molecular target for cancer diagnosis and intervention. Here, we labeled angiotensin II (Ang II), an AT1R ligand that is overexpressed in various solid cancers, with the near-infrared fluorescent dye, MPA, and radionuclide technetium-99m, and evaluated its capacity for HCC detection. These analyses were done in vitro using HepG2 (AT1R-positive) and BxPC3 (AT1R-negative) cell lines, and in vivo using a subcutaneous and orthotopic xenograft mouse model by fluorescence and SPECT imaging. Both Ang II-PEG₄-MPA- and [^99mTc]Tc-HYNIC-PEG₄-Ang II-bound AT1R exhibited a high affinity in vitro and [^99mTc]Tc-HYNIC-PEG₄-Ang II displayed an acceptable level of in vitro stability in rat plasma and whole blood. In vivo imaging revealed excellent specific tumor-targeting in HepG2 mouse xenografts models. In vitro and in vivo competition experiments revealed specific Ang II-PEG₄-MPA and [^99mTc]Tc-HYNIC-PEG₄-Ang II uptake by HepG2 cells and tumors. Altogether, AT1R-positive tumors were successfully detected via fluorescence and SPECT imaging using Ang II-PEG₄-MPA and [^99mTc]Tc-HYNIC-PEG₄-Ang II, respectively. Given their superior targeting capacity, Ang II-PEG₄-MPA and [^99mTc]Tc-HYNIC-PEG₄-Ang II are promising tools for HCC detection and warrant clinical translation.

中文翻译：

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AT1R特异的配体血管紧张素II作为肝细胞癌诊断的新型SPECT剂

肝细胞癌（HCC）的特点是死亡率高，因此迫切需要早期诊断和治疗。Ang II 1型受体（AT1R）最近已成为癌症诊断和干预的潜在分子靶标。在这里，我们用近红外荧光染料，MPA和放射性核素tech 99m标记了在多种实体癌中过表达的AT1R配体血管紧张素II（Ang II），并评估了其检测HCC的能力。这些分析是在体外使用HepG2（AT1R阳性）和BxPC3（AT1R阴性）细胞系进行的，在体内使用皮下和原位异种移植小鼠模型通过荧光和SPECT成像进行的。Ang II-PEG ₄ -MPA-和[ ^99m Tc] Tc-HYNIC-PEG ₄-Ang II结合的AT1R在体外表现出高亲和力，[ ^99m Tc] Tc-HYNIC-PEG ₄ -Ang II在大鼠血浆和全血中显示出可接受的体外稳定性水平。体内成像显示在HepG2小鼠异种移植模型中出色的特异性肿瘤靶向。体外和体内竞争实验表明，HepG2细胞和肿瘤可摄取特定的Ang II-PEG ₄ -MPA和[ ^99m Tc] Tc-HYNIC-PEG ₄ -Ang II。总之，分别使用Ang II-PEG ₄ -MPA和[ ^99m Tc] Tc-HYNIC-PEG ₄ -Ang II通过荧光和SPECT成像成功检测到了AT1R阳性肿瘤。鉴于其卓越的靶向能力，Ang II-PEG ₄-MPA和[ ^99m Tc] Tc-HYNIC-PEG ₄ -Ang II是用于HCC检测的有前途的工具，值得临床翻译。